Acetazolamide Found to Improve Decongestion in Patients With Acute Decompensated Heart Failure

New research suggests that acetazolamide and standard loop-diuretic therapy may decrease congestion and prevent future hospitalizations in patients with acute decompensated heart failure.

The addition of acetazolamide to loop-diuretic therapy is suggested to increase diuretic efficacy for patients with acute decompensated heart failure, according to a study published in the New England Journal of Medicine.

At the end of the trial, 78.8% of patients in the acetazolamide cohort had successful decongestion, compared to 62.5% of patients in the placebo group. Those treated with acetazolamide also had a shorter hospital stay, were less likely to have volume overload at discharge, and more diuresis and natriuresis.

“The addition of acetazolamide to standardized intravenous loop-diuretic therapy was associated with a higher incidence of successful decongestion within 3 days after randomization,” the study authors wrote.

Acetazolamide works by blocking proximal tubular sodium reabsorption into the body—in this respect, it acts as a diuretic. Acetazolamide may improve the efficacy of intravenous loop diuretics, which is recommended to mitigate fluid overload in patients with acute decompensated heart failure.

Researchers set out to evaluate whether acetazolamide successfully improved decongestion in patients with acute decompensated heart failure when it was added to intravenous loop-diuretic therapy.

The primary endpoint was defined as decongestion within 3 days of randomization without the requirement for more decongestive therapy. The key secondary endpoints were death from any cause or rehospitalization due to heart failure within 3 months of follow-up, and days from randomization until hospital discharge.

The team studied acetazolamide in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial, a multicenter, parallel-group, double-blind, randomized, and placebo-controlled study.

The ADVOR study enrolled 519 patients with acute decompensated heart failure. Participants also had clinical signs of volume overload, and N-terminal pro–B-type natriuretic peptide levels of more than 1000 pg per milliliter or more than 250 pg per milliliter.

Among the 256 patients who received acetazolamide with a loop-diuretic, 108 (42.2%) experienced congestion relief. Only 30.5% of patients in the placebo group experienced relief.

However, more patients died or were hospitalized for heart failure in the acetazolamide group compared to the placebo group, which affected 29.7% and 27.8% of patients, respectively.

Acetazolamide was found be a more efficient diuretic, increasing the cumulative urine output and natriuresis. Further, more patients in the evaluation group were discharged from the hospital without residual congestion.

The safety of both groups was found to be similar, with neither resulting in significantly worse adverse events. However, some limitations of the study include less generalization, since most participants were White. Additionally, the loop-diuretic doses were the same in both groups, and the study may not account for patients with newly diagnosed heart failure.

“The higher incidences of decongestion with acetazolamide treatment than with placebo were most probably related to the early and sustained increase in diuresis and natriuresis that were associated with the addition of acetazolamide,” the study authors concluded. “These findings highlight the importance of targeting congestion both early and aggressively and support the use of natriuresis as an indicator of diuretic response.”


Mullins, W., Dauw, J., Martens, P. et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. August 27, 2022. N Engl J Med 2022;387:1185-95. DOI: 10.1056/NEJMoa2203094